At baseline, participants had a mean age of 68 years and were predominately Caucasian and male as expected from university alumnae in 1939–1940. Mean BMI was 24.7kg/m2; 41% (n=985) had a BMI>25kg/m2 and 1.3% (n=31) <18.5kg/m2. Eight percent (n=190) smoked; 52% (n=1,213) were inactive. Pair-wise correlations between overweight and inactivity were −0.07 (p=0.34) among smokers and −0.06 (p=0.006) among nonsmokers.
Risk groups were composed as follows: Low (n=605, 25.9%); Medium (n=1,073; 46.1%); High (n=649; 27.9%). Cohort characteristics by risk group at baseline and last follow-up are shown in . Risk groups were comparable in gender, ethnicity, baseline age and years of education.
Demographic, Risk Factors, and Outcomes by Risk Group
By definition, low-risk participants met healthy BMI, smoking, and physical activity criteria at baseline. Medium-risk participants had a very low smoking rate (<5%); 41% had an abnormal BMI; and 55% did not exercise routinely. In contrast, 22% of high-risk subjects smoked, 89% had abnormal BMI, and only 3.5% exercised routinely. Walking pace was slower in the medium and high-risk groups when compared to the low-risk group. Baseline rates of hypertension, pulmonary disease, gastrointestinal disorders, arthritis and diabetes were higher in the high-risk compared to low-risk group. Prevalence of comorbidities was similar between groups.
Baseline HAQ-DI scores were low for all groups, although medium- and high-risk groups had higher scores than the low-risk group. The majority (75%) of participants had no disability. By the last observation, risk factor differences between groups had attenuated; although all comparisons remained significantly different between risk groups. Walking pace decreased and cumulative prevalence of comorbidies increased for all groups. With the exception of higher rates of hypertension and diabetes among high-risk participants, the cumulative prevalence of comorbidies did not differ significantly between risk groups.
Participants were observed for an average of 15.6 years. Age of survivors in 2005 was similar for all groups (85 years). Last observed HAQ-DI scores were significantly lower for the low-risk group compared to medium- and high-risk groups. Forty-eight percent of all study participants had died by 2005. Although age at death was similar, mortality rates were nearly 50% higher for high- compared to low-risk participants (384 vs. 248 per 10,000 person-years, p<0.001). Approximately 1% of participants, excluding decedents, were lost to follow-up each year. Those participants were 6 months younger with similar lower baseline HAQ-DI Scores.
displays yearly HAQ-DI scores by risk group. Disability increased each year in all groups. Participants without risk factors had the lowest HAQ-DI at each time point, followed by those with one risk factor. Differences were most pronounced at the later time points.
Unadjusted mean annual HAQ-DI disability scores by group. Diamond shape represents the low risk group (zero risk factors), triangle for medium risk group (one risk factor), and square for high risk group (two or three risk factors).
shows the dose-response relationship among groups in cumulative disability when comparing all participants, survivors, survivors without baseline disability, and by gender. Differences are most pronounced when comparing high- to low-risk participants. Cumulative disability, a surrogate for total lifetime disability, contains a bias in favor of the high risk group because of the shorter period during which disability accumulates. Similar results were seen when average disability was compared. Decedents had the highest average disability scores at all time points.
Cumulative disability (sum of annual HAQ-DI disability scores by risk group).
We compared Kaplan-Meier curves for the time for each group to attain a HAQ-DI of 1.0 (moderate disability) and death. The median time to develop moderate disability was approximately 8.0 years longer in the low-risk than the high-risk group (log-rank test p<0.0001).
Cox proportional hazard models adjusted for age, sex, and baseline disability yielded nearly identical findings. Compared to low-risk, the high-risk group had nearly a two-fold increased risk for the development of moderate disability (HAQ-DI=1) (HR 1.91, 95%CI 1.50–2.42), while medium risk participants had a 60% increased risk (HR 1.61, 95%CI 1.29–2.01). Age (HR 1.11, 95%CI 1.08–1.13) and higher baseline disability (HR 49.5, 95%CI 37–66) were also associated with disability.
The unadjusted probability of survival was significantly higher for low- compared to medium-and high-risk groups (). Curves separated early in the period of observation and continued to diverge over time. Sixty percent of the low-risk group was alive at 19 years compared to 53% and 43% in medium- and high-risk groups. The time to 20% mortality in each group was postponed by 3.6 years in low- versus high-risk participants; the postponement was 3.9 years to 40% mortality. Similar results were found when analyses were restricted to participants without baseline disability. Using survival analysis, medium- and high- risk participants had increased adjusted risks of mortality compared to low-risk (HR 1.18, 95%CI 1.01–1.37 and HR 1.47, 95%CI 1.25–1.73) although the differences were less marked compared with disability differences.
Kaplan-meier curve of probability of death by risk group
Multivariable Cox proportional hazards models were used to examine the relative role of each individual risk factor (abnormal BMI, smoking, and inactivity) as well as baseline walking pace and individual comorbidities upon moderate disability and mortality. Because the baseline HAQ-DI is among the strongest predictors of future disability and mortality, these analyses were restricted to the subset of participants (n=1,736) with baseline HAQ-DI=0 (). Males had an increased hazard of death (HR 1.47, 95%CI 1.18–1.81) but a reduced risk of disability (HR 0.52,95%CI 0.40–0.68). Among the three risk factors, smoking was associated with a two-fold increased risk of moderate disability (HR 2.02, 95%CI 1.32–3.08) and an even higher risk of death (HR 2.32, 95%CI 1.83–2.94). Faster walking pace was associated with a decrease in both morbidity and mortality. The presence of hypertension, diabetes, cardiovascular, pulmonary disease, stroke, or cancer at the baseline was associated with higher mortality; whereas only arthritis and stroke were associated with disability.
Association of Individual Risk Factors with Disability and Mortality (Participation with Zero Baseline Disability)
Since smoking as associated with the greatest risk for disability and mortality, we repeated the analysis on non-smokers (n=1,595). Neither having an abnormal BMI nor inactivity was significantly associated with disability or mortality in this smaller subset. Comorbid conditions and walking pace had similar effects upon disability and mortality in non-smokers.
Because of the possibility that death may be related to disability, and as such could present informational censoring over time26
, we repeated multi-variable proportional hazards modeling for disability among the 960 survivors. The magnitude of hazard ratios for covariates including individual risk factors, walking pace, and comorbidities was not substantially different than when decedents were include in the analysis (data not shown).
Population attributable risk for mortality and for moderate disability (HAQ-DI=1) were calculated for each risk factor and for individuals with ≥ 1 lifestyle risk factor (). Excess risk was seen for all risk groups for both mortality and moderate disability. Similar to the survival analysis, the highest attributable risk was seen with smoking.
Measures of Attributable Risk in the Population